This project will examine the effects on neuronal membrane lipid synthesis of toxic, xenobiotic agents widely distributed in the occupational and consumer environments. There are many people at risk of exposure to chemicals which are soluble in or are organic solvents. The long axoned neurons of the peripheral and central nervous systems are particularly vulnerable to these environmental toxic substances. Recent ultrastructural studies have suggested that a common mechanism of neuronal damage may produce similar characteristics and locations of the toxic actions of this diverse group of chemicals. The mechanism of the selective neuronal damage is unknown, but the toxic effects implicate the membrane systems of the neurons. We suggest that these toxic agents interact with cell membranes, damaging them or that they interfere with the synthesis of axonal membrane components which are primarily simple and complex lipids. Such effects have not yet been studied. The proposed work will test this possibility by a series of studies of increasing complexity that will compare the effects of known hydrocarbons on nervous tissue lipid synthesis to those of chemically related agents which are not specifically neuronotoxic. Studies of both in vitro and in vivo lipid synthesis and axonal transport have been planned. Several variables that can either interfere with the evaluation of such efforts or contribute to the damage are separately tested. These variables include the general and not neuronally specific toxicity of these agents and the production of toxic metabolites by other organs. Elucidation of a common biochemical pathological mechanism for the effects of these toxic substances should allow a unified approach to toxicity measurement, as well as to preventing or lessening damage after exposure.